This investigation will assess the acute safety, tolerance, and oral pharmacokinetics of escalating dosages of a kappa antagonist (JD-Tic), which has a slow onset (e.g. 4 hours with a peak at 24 hours) and very long duration of antagonism (e.g. 21-28 days). To assess kappa antagonism we will start with 10 subjects in a 4- day residential PILOT STUDY that will optimize the parameters of a kappa challenge using the agonist cyclazocine 0.8 mg orally along with naltrexone (12.5 mg oral). The kappa effects include diuresis, dysphoria, visual or cognitive distortion, sedation, analgesia and effects on the PCAG &LSD scales from the ARCI. Analgesia will be assessed using cold pressor and finger pressure tests to induce pain. This PILOT will be followed by 40 normal subjects in a month long COHORT STUDY with open, escalating JD-Tic dosing. We expect JD-Tic to attenuate these kappa effects in a dose related way when tested for this antagonism during a 4-day residential phase followed by a 3-week outpatient phase. Safety measurements include physical examinations, vital signs (BP, HR, RR, temperature) and 12-lead ECGs, hematology/serum, chemistry/urinalyses, psychometric determinations of cognitive function and affective state (e.g. depression and anxiety). Safety data will be analyzed by tabulation of symptoms and adverse events. A single dose of oral JD-Tic is given to four cohorts of 10 normals as: 15%, 30%, 45%, 60% of the maximally tolerated animal (primate) dose (MxTAD). Pharmacokinetic profiles, safety and efficacy assessments will be obtained taking into consideration JD-Tic's slow onset and very long duration of antagonism. After each dosage session subjects will be kept in a residential setting for 4 days followed by 3 weeks of twice weekly monitoring for continued kappa antagonist effects. After completion of the first cohort, the second will be started at the next highest dose (e.g. 30% MxTAD). The third cohort may be run at 60% MxTAD, if no kappa antagonism and minimal or no side effects occur at the 15% and 30% dosages. The final dosage may then be as high as 80% MxTAD. The two studies together involve 50 normals and lasts upto 4 weeks per COHORT subject. The JD-TIC dose optimization found in this study will determine dosing for the subsequent cocaine administration study.